# Tumor targeted engineered stem cells for treatment of lung cancer

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2021 · —

## Abstract

This proposal aims to explore and test a novel targeted oncolytic viro-cell therapy using the
mesenchymal stem cells (MSCs) infected by harmless common cold virus, the respiratory syncytial
virus (RSV) for treatment of lung cancers, which is the number one killer among cancers
worldwide. Despite advances in the treatment and improvement in outcomes, the 5-year survival
rates remain very poor (15% or less) for non–small cell lung cancers (NSCLC), which constitute
~85% of all lung cancer patients. Such poor survival rates combined with lung cancer
heterogeneity and development of resistance to classical chemo- and radio-therapies, underscore
the need for development of novel non-palliative therapeutic strategies. Though oncolytic
virotherapies have emerged as a potential alternative to traditional chemo- and radio-therapies,
their application to lung cancers remain limited. Also, inability to target oncolytic viruses to tumors
in general remains a critical barrier and particularly for lung cancers remains a major unmet need.
The motivation for the concept of targeted oncolytic viro-cell therapy against lung cancer comes
from two major developments. First, MSCs, a cell-type generally known to have intrinsic tumor
tropic properties, were found to be highly susceptible to RSV, with >90% infection rate, suggesting
the use of RSV-infected MSCs for both tumor targeting and tumor killing. This potential was
challenged by upregulation of indoleamine-2, 3-dioxygenase (IDO) by RSV-infected MSCs, which
suppresses tumor immunity and thus aid in tumorigenesis. However, it was found that IDO-
deficient hMSCs remain highly susceptible to RSV while alleviating the tumor suppressive effect.
Second, nonstructural protein 1 (NS1) deficient (ΔNS1) RSV replicates with high viral titer in lung
tumor cells, compared to the normal WI-38 diploid lung cells. Together these findings have led to
the hypothesis that the ∆NS1 RSV-infected IDO-deficient MSCs will retain tumor tropism and
would lend themselves to develop a targeted oncolytic viro-cell therapy against lung cancers. This
hypothesis will be tested in the following three specific aims. !
In aim #1, it is planned to develop and characterize a stable IDO-deficient hMSC cell line using the
CRISPR method and examine the anti-tumor activity potential of wild type and engineered (ΔNS1)
RSV-infected MSCs (RMSCs) in 3D multicell tumoroid cultures in vitro and biopsy-derived
tumoroids ex vivo. In aim #2, it is proposed to assess the anti-cancer potential of RMSCs in vivo in
immunocompetent syngeneic orthotopic model of lung cancer and evaluate their potential to
modulate anti-tumor immunity. In aim #3 the effects of RMSC in modulating apoptosis induced by
viral antigens will be investigated.
Overall, the targeted RMSC therapy is expected to provide a highly innovative and effective
approach for treatment of lung cancers. The PIs are uniquely positioned to conduct the proposed
studies to develop a novel therapeutic approach fo...

## Key facts

- **NIH application ID:** 10045941
- **Project number:** 5I01BX003413-04
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** SUBHRA MOHAPATRA
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045941

## Citation

> US National Institutes of Health, RePORTER application 10045941, Tumor targeted engineered stem cells for treatment of lung cancer (5I01BX003413-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10045941. Licensed CC0.

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